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Prevalence and risk factors of non-alcoholic fatty liver disease in HIV-monoinfection: a systematic review and meta-analysis
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Based on radiological criteria, our review found a prevalence of NAFLD in HIV monoinfectedof 35%.....The pooled prevalence of NASH was 41.7%
(95% CI 22.3 – 64.0).
In contrast to this our data suggests the prevalence of NAFLD in HIV-monoinfectedpatients may be higher (35%) than the general population (25%).
patients with HIV infection and features of the metabolic syndrome require afull diagnostic workup for NAFLD
Body mass index (MD 2.92 95%CI 2.14-3.70, p<0.00001), waist circumference (MD8.05 (5.46-10.64) p<0.00001), type 2 diabetes (OR 1.61 (1.09-2.39) p=0.02), hypertension (OR 1.75 (1.27-2.41) p=0.0006), high triglycerides (MD 61.52 (24.31-98.74) p=0.001), high total cholesterol (MD 6.19 (0.93-11.45) p=0.02), low HDLcholesterol (MD -4.21 (-6.82- -1.59) p=0.002), high LDL cholesterol (MD 5.80 (2.01-9.58) p=0.003), high fasting glucose (MD 0.43 (0.18-0.68) p=0.0007), high ALT (MD15.98 (8.04-23.92) p<0.0001), high AST (MD 5.27 (2.66-7.88) p<0.0001) and high CD4+ T cell count (MD 54.83 (11.55- 98.11) p=0.01) were associated with NAFLD.
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Prevalence and risk factors of non-alcoholic fatty liver disease in HIV-monoinfection: a systematic review and meta-analysis.
Maurice, James B; Patel, Amee; Scott, Alasdair J.; Patel, Krish; Thursz, Mark; Lemoine, Maud
AIDS June 1 2017
Objective: to identify the prevalence and risk factors of NAFLD, NASH and fibrosis in HIV-monoinfected patients.
Design: Systematic review and meta-analysis.
Methods: We searched Medline and Embase and included studies that enrolled
HIV-monoinfected patients with NAFLD defined by imaging and/or liver histology. Data on prevalence and risk factors for NAFLD, NASH and fibrosis were collected for meta-analysis using random effects models.
Results: Ten studies were included from USA (n = 4), Canada (n = 1), France (n = 2), Italy (n = 1), Japan (n = 1) and China (n = 1). The prevalence of NAFLD (Imaging studies), NASH and fibrosis (biopsied populations) were 35% (95% CI 29-42), 42% (95% CI 22-64) and 22% (95% CI 13-34), respectively. Meta-analysis of risk factors showed high BMI, waist circumference, type 2 diabetes, hypertension, triglycerides and high CD4 cell count were associated with NAFLD, whereas HIV viral load, duration of HIV infection, duration of ART and CD4 nadir were not. Patients with high BMI (MD 1.38 95% CI 0.04-2.71 p = 0.04), fasting glucose (MD 0.80 95% CI 0.47-1.13 p < 0.00001) and AST level (MD 13.00 95% CI 4.34-21.65 p = 0.003) were at increased risk of significant liver fibrosis.
Conclusions: NAFLD is frequently observed in HIV-monoinfected patients, and NASH is a common cause of unexplained abnormal liver function in patients selected for liver biopsy. Metabolic disorders are key risk factors independently of HIV parameters. Future trials on pharmacological interventions in NASH with fibrosis should include patients with HIV.
Conclusion
NAFLD is common in HIV-monoinfected patients. Metabolic disorders are key risk factors of NAFLD independent of HIV parameters and predict its complications. The strong association between obesity and liver fibrosis in HIV-monoinfected patients supports the adipocentric concept of liver fibrogenesis in this population. This needs to be confirmed by additional studies. Our systematic review underlines the need for additional data on NAFLD in HIV infection as well as a better standardized assessment and management of the disease.
Based on radiological criteria, our review found a prevalence of NAFLD in HIV monoinfectedof 35%.
In contrast to this our data suggests the prevalence of NAFLD in HIV-monoinfectedpatients may be higher (35%) than the general population (25%).
patients with HIV infection and features of the metabolic syndrome require afull diagnostic workup for NAFLD
the management of dyslipidaemia,hypertension, diabetes mellitus and obesity in a multi- disciplinary setting is therefore an essential aspect of HIV care, and is already an integral service offered to patientsin many centres.This needs to be combined with effective liver assessment and riskstratification with non- invasive tools such as transient elastography and/orbiochemical markers (e.g. Enhanced Liver Fibrosis (ELF) score and NAFLD fibrosisscore),[31] to identify patients who need more dedicated input from a specialisthepatologist
Both NAFLD and HIV also confer increased risk ofcardiovascular disease.[30] Therefore the management of dyslipidaemia,hypertension, diabetes mellitus and obesity in a multi- disciplinary setting is thereforean essential aspect of HIV care, and is already an integral service offered to patientsin many centres.
There was insufficient data to meta- analyse exposure by drug class.
Only the studyby Guaraldi et al identified cumulative NRTI exposure to be associated with NAFLD.
This was in a population with a median exposure of 124 months, and given the timeperiod this may have included hepatotoxic 'D-drugs' (didanosine, zalcitabine andstavudine), although this is not specified in the paper.[21] Four other studies in thereview examined drug class exposure and found no association with NAFLD[15][18][22][23]
It is debated how this compares to the general population; Vodkin et al. showed a
higher rate of NASH in HIV patients (64 vs 36%),[8] whereas a recent systematic
review reported similar results in biopsied cohorts (59%).[4] The significant statistical heterogeneity between studies reflects the small and varied study populations, which makes an accurate study of the prevalence of severe disease difficult. This is exacerbated in the assessment of NASH by the evolution of histological definitions of the disease over the last 10 years, and one included study used a definition of NASH now not widely used, which may partly explain the unusually low prevalence (7%) in that study.[15]
Taken together, these results warrant three comments. First, imaging studiessuggest NAFLD is common in HIV-monoinfected patients but limited histological datawithout long term follow-up on the incidence of NASH/fibrosis in the post- HAARTera mean we still do not know what the rate is of fibrosis progression as compared toHIV- negative patients with NAFLD. It is possible that while metabolic factorspredominate in disease pathogenesis, HIV infection and/ or drug exposure couldpotentiate the effects in the liver such that disease progresses with milder features ofthe metabolic syndrome, which may explain why some studies show NAFLDoccurring in HIV- infected patients with lower BMI.[28] However, to address thisquestion longitudinal studies with good quality histological data are needed.
Second, patients with HIV infection and features of the metabolic syndrome require a full diagnostic workup for NAFLD. The prevalence of NAFLD is rising rapidly in the Western world in parallel with increasing obesity and the metabolic syndrome, andhas become a prominent cause of liver- related morbidity and requirement for livertransplantation.[29] Both NAFLD and HIV also confer increased risk of cardiovascular disease.[30] Therefore the management of dyslipidaemia,hypertension, diabetes mellitus and obesity in a multi- disciplinary setting is therefore an essential aspect of HIV care, and is already an integral service offered to patientsin many centres. This needs to be combined with effective liver assessment and riskstratification with non- invasive tools such as transient elastography and/orbiochemical markers (e.g. Enhanced Liver Fibrosis (ELF) score and NAFLD fibrosisscore),[31] to identify patients who need more dedicated input from a specialist hepatologist. However, the performance of these tools has been poorly validated inHIV mono-infected patients, and the disparity between estimates of fibrosis in thestudies reporting both FIB-4 and transient elastography data highlights this point.
Third, we are entering a new era in the management of NAFLD. The mainstay oftreating the disease has long been based on life style modification including weightloss and physical activity[32]. However only a small proportion of patients successfully achieve this. Fortunately multiple new treatments are emerging for advanced disease.[33] Yet HIV infection is invariably an exclusion factor for patientsenrolled in these trials. The data from this review shows how therapeutic options areat least as important in patients with HIV, and it is essential such trials do notexclude HIV patients.
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